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https://www.readbyqxmd.com/read/29692000/phloroglucinol-derivatives-from-the-fruits-of-eucalyptus-globulus-and-their-cytotoxic-activities
#1
Pham Thi-Anh, Imran Shair Mohammad, Vu Van-Tuan, Hu Xiao-Long, Chaurasiya Birendra, Aftab Ulah, Guo Cui, Lv Xian-Yu, Ye Wen-Cai, Wang Hao
A new phloroglucinol derivative, named Eucalyptin B (1), along with five related known compounds (2-6), was isolated from the fruits of Eucalyptus globulus. Their structures were elucidated by means of 1D and 2D NMR spectroscopy, with the absolute configuration of 1 determined by electronic circular dichroism (ECD) calculations. All isolated compounds (1-6) were evaluated for their cytotoxic activities against lung (A549), breast (4T1), and skin (B16F10) cancer cell lines. On the basis of cytoxicity the antitumor activity of Eucalyptin B (1) was further confirmed by apoptosis assay...
April 24, 2018: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/29691981/up-regulation-of-mir-10b-3p-promotes-the-progression-of-hepatocellular-carcinoma-cells-via-targeting-cmtm5
#2
Lianyue Guan, Degang Ji, Na Liang, Shuo Li, Baozhen Sun
In this study, we investigated how miR-10b-3p regulated the proliferation, migration, invasion in hepatocellular carcinoma (HCC) at both in vitro and in vivo levels. CMTM5 was among the differentially expressed genes (data from TCGA). The expression of miR-10b-3p and CMTM5 was detected by qRT-PCR and Western blot (WB). TargetScan was used to acquire the binding sites. Dual-luciferase reporter gene assay was used to verify the direct target relationship between miR-10b-3p and CMTM5. WB analysis proved that miR-10b-3p suppressed CMTM5 expression...
April 24, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29691980/glucocorticoids-modulate-multidrug-resistance-transporters-in-the-first-trimester-human-placenta
#3
Phetcharawan Lye, Enrrico Bloise, Lubna Nadeem, William Gibb, Stephen J Lye, Stephen G Matthews
The placental multidrug transporters, P-glycoprotein (P-gp, encoded by ABCB1) and breast cancer resistance protein (BCRP, ABCG2) protect the foetus from exposure to maternally derived glucocorticoids, toxins and xenobiotics. During pregnancy, maternal glucocorticoid levels can be elevated by stress or exogenous administration. We hypothesized that glucocorticoids modulate the expression of ABCB1/P-gp and ABCG2/BCRP in the first trimester human placenta. Our objective was to examine whether dexamethasone (DEX) or cortisol modulate first trimester placental expression of multidrug transporters and determine whether cytotrophoblasts or the syncytiotrophoblast are/is responsible for mediating these effects...
April 24, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29691845/establishment-of-a-new-fish-cell-line-from-the-caudal-fin-of-golden-pompano-trachinotus-ovatus-and-its-susceptibility-to-iridovirus
#4
S Wei, Y Yu, Q Qin
A new cell line derived from the caudal fin of golden pompano Trachinotus ovatus (TOCF) was successfully established and characterized. TOCF cells grew well at 28° C in L-15 medium supplemented with 10% foetal bovine serum (FBS). The cell line has been subcultured in more than 100 passages. Molecular characterization of 18S ribosomal (r)RNA and cytochrome oxidase subunit 1 (COI) confirmed that the TOCF cells were derived indeed from T. ovatus. TOCF cells have a modal chromosome number of 54. It was further showed that TOCF cells were transfected successfully with pEGFP-N3 and pDsRED-N1 plasmid, suggesting that TOCF cells could be used to research gene functions in vitro...
April 24, 2018: Journal of Fish Biology
https://www.readbyqxmd.com/read/29691780/combinatory-rna-sequencing-analyses-reveal-a-dual-mode-of-gene-regulation-by-adar1-in-gastric-cancer
#5
Charles J Cho, Jaeeun Jung, Lushang Jiang, Eun Ji Lee, Dae-Soo Kim, Byung Sik Kim, Hee Sung Kim, Hwoon-Yong Jung, Ho-June Song, Sung Wook Hwang, Yangsoon Park, Min Kyo Jung, Chan Gi Pack, Seung-Jae Myung, Suhwan Chang
BACKGROUND: Adenosine deaminase acting on RNA 1 (ADAR1) is known to mediate deamination of adenosine-to-inosine through binding to double-stranded RNA, the phenomenon known as RNA editing. Currently, the function of ADAR1 in gastric cancer is unclear. AIMS: This study was aimed at investigating RNA editing-dependent and editing-independent functions of ADAR1 in gastric cancer, especially focusing on its influence on editing of 3' untranslated regions (UTRs) and subsequent changes in expression of messenger RNAs (mRNAs) as well as microRNAs (miRNAs)...
April 25, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29691753/bioactivity-safety-and-efficacy-of-amphotericin-b-nanomicellar-aerosols-using-sodium-deoxycholate-sulfate-as-the-lipid-carrier
#6
Faisal Usman, Ruqaiya Khalil, Zaheer Ul-Haq, Titpawan Nakpheng, Teerapol Srichana
We report nanomicelles of amphotericin B (AmB) using various molar ratios of AmB and sodium deoxycholate sulfate (SDCS) for inhalation with improved stability, solubility, bioactivity, and safety. The particle sizes of all aerosolized formulations are expressed as mass median aerodynamic diameter (0.9-1.6 μm), fine particle fraction (70.3-86.5%), and geometric standard deviation (1.4-2.1) which indicated their sizes are appropriate for use as an inhaler. In vitro cytotoxicity studies conducted using respiratory and kidney cell lines demonstrated that the marketed Fungizone® was toxic to macrophage and embryonic kidney cells and cell viability decreased from 96 to 48% and from 97 to 67%, respectively when the AmB equivalent concentration was increased from 1 to 16 μg/mL...
April 24, 2018: AAPS PharmSciTech
https://www.readbyqxmd.com/read/29691708/generation-of-insulin-deficient-piglets-by-disrupting-ins-gene-using-crispr-cas9-system
#7
Bumrae Cho, Su Jin Kim, Eun-Jin Lee, Sun Mi Ahn, Jin Seok Lee, Dal-Young Ji, Kiho Lee, Jung-Taek Kang
Diabetes mellitus is a chronic disease with accompanying severe complications. Various animal models, mostly rodents due to availability of genetically modified lines, have been used to investigate the pathophysiology of diabetes. Using pigs for diabetic research can be beneficial because of their similarity in size, pathogenesis pathway, physiology, and metabolism with human. However, the use of pigs for diabetes research has been hampered due to only few pig models presenting diabetes symptoms. In this study, we have successfully generated insulin-deficient pigs by generating the indels of the porcine INS gene in somatic cells using CRISPR/Cas9 system followed by somatic cell nuclear transfer...
April 24, 2018: Transgenic Research
https://www.readbyqxmd.com/read/29691586/-the-role-of-adventitia-in-hypoxic-vascular-remodeling
#8
Fu-Yang Yu, Sheng-Chang Yang, En-Sheng Ji
As an important site for the production, storage and release of key regulators for vascular function, the vascular adventitia is thought to be a damage sensing tissue in the vascular wall under certain conditions. The adventitial cells are usually the first ones to respond to vascular stress or injury, and consequently affect the structure and function of blood vessel wall. Growing lines of evidence have shown that the vascular adventitia exhibits the earliest and most prominent changes in vascular remodeling due to hypoxia and related pulmonary hypertension and atherosclerosis...
April 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/29691583/-establishment-and-characterization-of-a549-tumor-monoclonal-cell-line-with-uchl1-gene-deletion
#9
Yu Zhang, Yan Shi, Di Song, Xuan Zhang, Lin Yu, Ya-Ping He, Zhao-Gui Sun
The purpose of this study was to investigate the effects of ubiquitin C-terminal hydrolase-L1 (UCHL1) on non-small cell lung cancer cell line A549. UCHL1 gene knockout A549 cell line was constructed by CRISPR-CAS9 gene editing technique. The mRNA and protein levels of UCHL1 were examined by RT-PCR and Western blot, respectively. Cell proliferation and cycles were analyzed by CCK-8 method and flow cytometry, respectively. The sensitivity of A549 cells to cisplatin was detected by CCK-8 method. Migration ability of A549 cells was detected by scratch assay and Transwell test, and p-Erk expression level was assessed by Western blot...
April 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/29691578/-effects-of-thyroid-hormone-on-macrophage-dysfunction-induced-by-oxidized-low-density-lipoprotein
#10
Yu Ning, Ming Zhang, Yun-Hui DU, Hui-Na Zhang, Lin-Yi Li, Yan-Wen Qin, Wan-Wan Wen, Quan-Ming Zhao
It has been recognized that patients with hypothyroidism have higher risks of atherosclerosis and coronary heart disease, however, the mechanisms are largely unknown. Considering that macrophage dysfunction plays an important role in the formation and development of atherosclerosis plaques, this study aimed to investigate the direct effects of thyroid hormone on macrophage functions and to provide new insight for the mechanism of hypothyroid atherosclerosis. RAW264.7 cells (mouse leukaemic monocyte macrophage cell line) were incubated with oxidized low-density lipoprotein (oxLDL) to establish macrophage foam cells model in vitro, and the protective effects of different concentration of thyroxine (T4) on the macrophage foam cells function were explored...
April 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/29691546/darzens-reaction-of-thioisatins-and-sulfonium-salts-approach-to-the-synthesis-of-thiochromenone-derivatives-with-anticancer-potency
#11
Jinhui Shen, Yang Yang, Xiaoli Hou, Wenlei Zeng, Aimin Yu, Xiaowei Zhao, Xiangtai Meng
A new Darzens reaction of thioisatins and sulfonium salts has, for the first time, been reported. This reaction allows efficient access to thiochromenone derivatives in good to excellent yields under mild reaction conditions. The substrate scope includes both electron-withdrawing and electron-donating groups on both the thioisatins and sulfonium salts. Moreover, some of the synthesized thiochromenone derivatives have been found to show potent anticancer activities against six different cancer cell lines using the methylthiazoltetrazolium (MTT) assay...
April 25, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29691484/hamuramicins-a-and-b-22-membered-macrolides-produced-by-an-endophytic-actinomycete-allostreptomyces-sp-k12-0794
#12
Takuya Suga, Tōru Kimura, Yuki Inahashi, Masato Iwatsuki, Kenichi Nonaka, Akira Také, Atsuko Matsumoto, Yōko Takahashi, Satoshi Ōmura, Takuji Nakashima
Two new compounds, designated as hamuramicins A (1) and B (2), were isolated from the cultured broth of an endophytic actinomycete Allostreptomyces sp. K12-0794 by silica gel column chromatography and HPLC. The structures of 1 and 2 were elucidated as 22-membered macrolide containing triene and trienone with an alkyl side chain by spectroscopic analyses including NMR experiments. Both compounds showed growth inhibition activity against Kocuria rhizophia and Xanthomonas oryzae pv. oryzae as well as human cell line toxicity...
April 24, 2018: Journal of Antibiotics
https://www.readbyqxmd.com/read/29691338/the-efficacy-of-the-interferon-alpha-beta-response-versus-arboviruses-is-temperature-dependent
#13
Whitney C Lane, Matthew D Dunn, Christina L Gardner, L K Metthew Lam, Alan M Watson, Amy L Hartman, Kate D Ryman, William B Klimstra
Interferon alpha/beta (IFN-α/β) is a critical mediator of protection against most viruses, with host survival frequently impossible in its absence. Many studies have investigated the pathways involved in the induction of IFN-α/β after virus infection and the resultant upregulation of antiviral IFN-stimulated genes (ISGs) through IFN-α/β receptor complex signaling. However, other than examining the effects of genetic deletion of induction or effector pathway components, little is known regarding the functionality of these responses in intact hosts and whether host genetic or environmental factors might influence their potency...
April 24, 2018: MBio
https://www.readbyqxmd.com/read/29691295/metformin-targets-mitochondrial-glycerophosphate-dehydrogenase-mgpdh-to-control-rate-of-oxidative-phosphorylation-and-growth-of-thyroid-cancer-in-vitro-and-in-vivo
#14
Joanna Klubo-Gwiezdzinska, Shilpa Thakur, Brianna Daley, Kelli Gaskins, Vasyl V Vasko, Myriem Boufraqech, Dhaval Patel, Carole Sourbier, Jeff M Reece, Sheue-Yann Cheng, Electron Kebebew, Sunita K Agarwal
PURPOSE: Mitochondrial glycerophosphate dehydrogenase (mGPDH) is the key enzyme connecting oxidative phosphorylation (OXPHOS) and glycolysis as well as a target of the antidiabetic drug metformin (MF) in the liver. There are no data on the expression and role of mGPDH as a metformin target in cancer. In this study, we evaluated mGPDH as a potential target of metformin in thyroid cancer and investigated its contribution in thyroid cancer metabolism. EXPERIMENTAL DESIGN: We analyzed mGPDH expression in 253 thyroid cancer and normal tissues by immunostaining and examined its expression and localization in thyroid cancer-derived cell lines (FTC133, BCPAP) by confocal microscopy...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29691292/phenformin-induced-mitochondrial-dysfunction-sensitizes-hepatocellular-carcinoma-for-dual-inhibition-of-mtor
#15
Sonia Rosa Veiga, Xuemei Ge, Carol A Mercer, María Isabel Hernández-Alvarez, Hala Elnakat Thomas, Javier Hernández-Losa, Santiago Ramón Y Cajal, Antonio Zorzano, George Thomas, Sara C Kozma
PURPOSE: Hepatocellular carcinoma (HCC) ranks second in cancer mortality and has limited therapeutic options. We recently described the synergistic effect of allosteric and ATP-site competitive inhibitors against the mammalian target of rapamycin (mTOR) for the treatment of HCC. However, such inhibitors induce glycemia and increase mitochondrial efficiency. Here we determined whether the mitochondrial complex I inhibitor Phenformin could reverse both side effects, impose an energetic-stress on cancer cells and suppress the growth of HCC...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29691287/systematic-modelling-and-design-evaluation-of-unperturbed-tumour-dynamics-in-xenografts
#16
Zinnia P Patricia Parra Guillen, Victor Mangas Sanjuan, Maria Garcia-Cremades, Inaki F Troconiz, Gary Mo, Celine Pitou, Philip W Iversen, Johan E Wallin
Xenograft mice are largely used to evaluate the efficacy of oncological drugs during preclinical phases of drug discovery and development. Mathematical models provide a useful tool to quantitatively characterise tumour growth dynamics and also optimise upcoming experiments. To the best of our knowledge, this is the first report where unperturbed growth of a large set of tumour cell lines (n=28) has been systematically analysed using the model proposed by Simeoni in the context of non-linear mixed effect (NLME)...
April 24, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29691279/assessment-of-the-molecular-mechanisms-of-action-of-novel-4-phenylpyridine-2-one-and-6-phenylpyrimidin-4-one-allosteric-modulators-at-the-m1-muscarinic-acetylcholine-receptors
#17
Emma T van der Westhuizen, Arthur Spathis, Elham Khajehali, Maneula Jorg, Shailesh N Mistry, Ben Capuano, Andrew B Tobin, Patrick M Sexton, Peter J Scammells, Celine Valant, Arthur Christopoulos
Positive allosteric modulators (PAMs) that target the M1 muscarinic acetylcholine (ACh) receptor (M1 mAChR) are potential treatments for cognitive deficits in conditions such as Alzheimer's disease and schizophrenia. We recently reported novel 4-phenylpyridine-2-one and 6-phenylpyrimidin-4-one M1 mAChR PAMs with the potential to display different modes of positive allosteric modulation and/or agonism (Mistry et al., 2016), but their molecular mechanisms of action remain undetermined. The current study compared the pharmacology of three such novel PAMs with the prototypical first-generation PAM, BQCA, in a recombinant Chinese hamster ovary (CHO) cell line stably expressing the human M1 mAChR...
April 24, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29691239/disposition-of-mianserin-and-cyclizine-in-ugt2b10-overexpressing-hek293-cells-identification-of-ugt2b10-as-a-novel-n-glucosidation-enzyme-and-bcrp-as-an-n-glucoside-transporter
#18
Danyi Lu, Dong Dong, Qian Xie, Zhijie Li, Baojian Wu
UDP-glucuronosyltransferases (UGTs) play an important role in metabolism and detoxification of amine-containing chemicals. However, the disposition mechanisms for amines via UGT metabolism are not fully clear. Here we aim to investigate a potential role of UGT2B10 in N-glucosidation, and to determine the transporters for excretion of N-glucosides. We first established a HEK293 cell line stably overexpressing UGT2B10. Incubation of mianserin or cyclizine with the cells generated one N-glucuronide and one N-glucoside...
April 24, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29691238/structure-activity-relationships-of-the-main-bioactive-constituents-of-euodia-ruticarpa-on-aryl-hydrocarbon-receptor-activation-and-bile-acid-homeostasis
#19
Youbo Zhang, Tingting Yan, Dongxue Sun, Cen Xie, Yiran Zheng, Lei Zhang, Tomoki Yagai, Kristopher W Krausz, William H Bisson, Xiuwei Yang, Frank J Gonzalez
Rutaecarpine (RUT), evodiamine (EOD) and dehydroevodiamine (DHED), are the three main bioactive indoloquinazoline alkaloids isolated from Euodia ruticarpa, a widely prescribed traditional Chinese medicine. Here, the structure-activity relationships of these analogues for aryl hydrocarbon receptor (AHR) activation were explored by use of Ahr-deficient (Ahr-/-) mice, primary hepatocyte cultures, luciferase reporter gene assays, in silico ligand docking studies and metabolomics. In vitro, both mRNA analysis of AHR target genes in mouse primary hepatocytes and luciferase reporter assays in hepatocarcinoma cell lines demonstrated that RUT, EOD and DHED significantly activated AHR, with an efficacy order of RUT > DHED > EOD...
April 24, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29691234/drug-induced-senescent-multiple-myeloma-cells-elicit-nk-cell-proliferation-by-direct-or-exosome-mediated-il-15-trans-presentation
#20
Cristiana Borrelli, Biancamaria Ricci, Elisabetta Vulpis, Cinzia Fionda, Maria Rosaria Ricciardi, Maria Teresa Petrucci, Laura Masuelli, Agnese Peri, Marco Cippitelli, Alessandra Zingoni, Angela Santoni, Alessandra Soriani
Treatment of multiple myeloma (MM) cells with sub-lethal doses of genotoxic drugs leads to senescence and results in increased NK cell recognition and effector functions. Herein we demonstrated that doxorubicin- and melphalan-treated senescent cells display increased expression of IL15, a cytokine involved in NK cell activation, proliferation, and maturation. IL15 up-regulation was evident at the mRNA and protein level, both in MM cell lines and malignant plasma cells (PCs) from patients' bone marrow (BM) aspirates...
April 24, 2018: Cancer Immunology Research
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